Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B

In the reported Asian lamivudine trial, the rate of hepatitis B e antigen ( HBeAg) seroconversion, defined as HBeAg/hepatitis B virus (HBV) DNA serocle arance and development of anti-HBe, during 52 weeks of treatment was only 1 3% to 16%. To evaluate whether any factors influenced HBeAg seroconversion, data from 345 patients in that trial were reanalyzed to correlate HBeAg se roconversion with variables including treatment, age, gender, body build, h istology, baseline HBV-DNA levels, and alanine transaminase (ALT) levels. E xploratory analysis using stepwise modeling revealed that HBeAg seroconvers ion correlated highly with pretherapy ALT (P <.001) followed by lamivudine therapy (P =.013), but only marginally with baseline HBV-DNA (P =.071) and cirrhosis (P =.066) for lamivudine 100 mg and placebo comparison, Among the se four variables, only pretherapy ALT still had a highly significant (P <. 001) correlation and lamivudine therapy had a borderline association (P =.0 66) for lamivudine 25 mg and placebo comparison. Categorical analysis revea led that HBeAg seroconversion occurred earlier and the cumulative rate was significantly higher in patients with pretherapy ALT values over 2 times th e upper limit of normal (ULN) as compared with treated patients with lower ALT levels or untreated control patients with the same ALT levels (P <.001, respectively). The highest HBeAg seroconversion rate was observed in 100 m g lamivudine-treated patients with ALT levels greater than 5 times the ULN (64%) compared with patients with ALT 2 to 5 times the ULN (26%, P =.03); a nd ALT less than 2 times the ULN, (5%, P <.001). These results suggest that pretherapy ALT is the strongest determinant for HBeAg seroconversion durin g lamivudine therapy, and should be considered in selecting patients for tr eatment.